SU398038A1 - METHOD OF OBTAINING DERIVATIVES - Google Patents

Description

This invention relates to a process for the preparation of new derivatives of p-aminoalkylbenzenesulfones .id having valuable pharmacolic properties. II Ег-О-С-ЁГ-СНг-СН

where RI is cyclopentyl or cyclohexyl; five

R2 - unbranched or branched

Ng-SNg-SNg -

process

where RI is as above, a compound of the general formula

ABOUT

II RS-O-C-X

where R2 is as defined above, X is a halogen, or acyloxy group, which is a residue of the mono-ether of carbonic acidic C2-C4 alkyl, or their salts, in that the compound of the general formula

you, with the subsequent isolation of the target product in free form or in the form of a salt by known methods.

The reaction is carried out at (-20) - + 20 ° C, preferably in an inert organic solvent, for example benzene, toluene, xylene, ether, dioxane, tetrag.idrofuran, methylene chloride, acetone or methyl ethyl ketone.

Chloroformic acid ester is introduced into the reaction, preferably in the presence of an amine based on the known acylation reaction, the proposed method of obtaining derivatives (g- (2-amino-eth; 1l) -be} 13olsulfones. Of the general formula

an acid receptor, such as inorganic bases or salts, for example, hydroxy acids, acetates, bicarbonates, carbonates and phosphates of alkali metals, in particular sodium or potassium. Oxide, carbonate sludge, and calcium phosphate, as well as magnesium carbonate, can be used for this purpose. Instead of inorganic compounds or salts, organic bases can be used, for example, pyridine, trimetnlamine, triethylamine, diisopronylamine or collidine, the excess of which can serve as a solvent.

Instead of amines of the above formula, sodium, potassium or lithium derivatives substituted in nitrogen can be used.

Source amines. Can be obtained, for example, by the interaction of sulfonic anhydride of the general formula

SOo-Cl

lower alkyl or phenyl, with 2-amino-2-imidazoline total

gp

Y

where Ri is as indicated above, followed by hydrolytic cleavage of a | Tsilna protective group.

The starting amines can also be obtained from p- (aminoethyl) benzene sulfopamide, synthesized according to Miller, and the substituted N- (2bromoethyl) cyanamide in an alkaline medium.

Esters of chloroformic acid are obtained by known methods.

Example I. To a solution of 42.4 g of (2-aminoethyl) -phenylsulfonyl 2-imino-3-cy1 Cyclohexylimidazolide dihydrochloride, t. Pl. 247-250 ° C, 120 ml of 2N are added to 50 ml of water. caustic soda, the precipitated free base is extracted with 3X100 ml of methylene chloride, the extract is dried with sodium sulfate, mixed with 11 g of triethylamine and transferred to a dropping funnel. A solution of 10.8 g of ethyl chloroformate in 100; l of methylene chloride is poured into another dropping funnel. The solutions are poured into the reactor from dropping vorono.k with stirring and O-10 ° C at such a rate that equimolar quantities of reagents are supplied per unit time. The mixture is stirred at room temperature for 1 hour, the solution is washed with water, the methylene chloride is distilled off with sodium sulfate and 1 - ((ethoxycarbon, ylamido) ethyl phenylsulfonyl} -2-, imino-3-cyclohexylimidizolidine, m.p. ° C (ethyl acetate).

In order to obtain the starting dihydrochloride. (Aminoetyl) phenylsulfonyl -2-imino-3-cyclohexylimidazolidine, 20.3 g of 1-cyclohexyl-2-imino-imidazolidine hydrochloride prepared in a solution of 8.5 g of caustic soda in 85 ml of water was added. the solution is treated with a solution of 26.6 g of L- (2-acetamidoethyl) -benzenesulfonyl chloride in 100 ml of acetone (exothermic reaction), heated for 0.5 hour to

90 ° C and evaporated in vacuo to dryness, the residue of p-(2-acetamidoethyl) -phenylsulfonyl-2-imino-3-cyclohexylimidazolidine is recrystallized from ethyl acetate.

To synthesize the starting p- (2-acetamidoethyl) benzene sulfonyl chloride in 35 g of chlorosulfonic acid, 16.3 g of N-phenethylacetatemide are added with stirring, heated for 2 hours at 60 ° C and stirred, poured onto ice, the product is filtered off, dried in vacuum and

used without purification for further syntheses.

A solution of 39.3 g of (2-acetam.midoethyl) -phenylsulfonyl-2-imino-3-cyclohexylimidazolidine in 370 g of 2 n. hydrochloric acid is boiled for 6 hours under reflux, evaporated in vacuo, the remaining oil is treated with warm ethanol. m and after cooling the dihydrochloride (2-a.minoethyl) phenylsulfopyl-2-imino-3-cyclotexylimidazolidine, m.p. . 247-250 ° C.

Example 2. Analogously to Example 1, using in each case 41 g of dihydrochloride (2-aminoethyl) -fen, ylsulfonyl) -2-imino-3-cycloylmethylimidazolide; ina, mp. 270 ° C

(decomp.), obtained from 10.9 g of ethyl ether of chloroformic acid 1- {p. (ethoxycarbonylamino) -ethyl-phenylsulfonyl -2-: imino3-cycloylphenyl imidazolidine, t. Il. 111-112 ° C; from 12.3 g of isopropyl chloroformate-1- {(isopropyloxycarbonylamino-ethyl-phenylsulfonyl) -2-imino-3-cyclopentylimidazolidine, m.p. 167-168 ° C; from 13.7 g of butyl chloroformate-1- (butoxycarbonylamio) -ethyl-phonylsulfonyl -2-imino-3-cycloienthiene. imidazolidine, t.nl. 1 4-115 ° C; from 13.7 g of isobutyl chloroformate ester - 1 .. I (isobutoxycarbonylamino) -ethyl-phenylsulfonyl) -2-.and: .oino-3-diclopentylimidazolidine, t. pl. 144-145 ° C.

Example 3. As in example 1, from 42.4 g of dihydrochloride (2-aminoethyl) is phenylsulfonyl -2-imino-3-cyclohexylimidazolidine, m.p. 247-250 ° С, and 13.7 g of butyl chloroformate are obtained for 1- {(butoxycarbonyl.mino) -ethyl-phenyl., Sulfonyl-2-i.mino-3-cyclohexylimidazolidine, t. Ll. 123-124 S.

Subject invention

1. A process for the preparation of p- (2-amino-ethyl) -benzenesulfonamide derivatives of the general formula

where Ri is cyclopentll or cyclohexyl; R2 - unbranched or branched C-C4NH

alkyl, or salts thereof, characterized in that the compound of the general formula

where RI is like a; chazano above, is treated with a compound of the general formula

O 11 R2-0-C-X where R2 is as defined above, X is X-halo or axyloxy group obtained from a mono-ether of carbonic acid, followed by isolation of the desired product in the free state or as a salt with known iriemems.

2. The method according to and. 1, is different because the process is conducted in an inert organic solvent. 3. Method according to pi. 1 and 2, characterized in that the process is carried out in an extruder and an acid acceptor.